Data is collected and has been analyzed from four participants carrying compound-inactivating variants in Piezo2. Healthy control participants were also tested for comparison. Piezo2 is a expressed in some somatosensory neurons and in Merkel cells. Piezo2 is essential for discriminative aspects of touch and for proprioception. Through detailed sensory testing the role of this protein can be further characterized and the related mechanosensory deficits better understood. Data were also collected from a second participant with deafferentation of large diameter myelinated afferents (the first was tested the previous reporting year) producing a clinical condition with a lack of discriminatory touch and proprioception. Data from these participants were compared to data collected from neurologically intact individuals as well as to the 4 participants carrying compound-inactivating variants in Piezo2 described above. Quantitative sensory testing and functional brain imaging data collection from a patient with congenital insensitivity to pain and matched controls is underway. The pain insensitive patient has no known genetic mutations or gross central structural abnormalities that would account for the perceptual pain deficit. Through systematic sensory testing aimed at investigating specific nerve fiber function, receptors, and central versus peripheral pathways we can better characterize the patient's condition which could have implications for developing new methods of pain modulation.